Population pharmacokinetics of ketanserin in pre-eclamptic patients and its association with antihypertensive response.

Abstract

Ketanserin is an antihypertensive drug that is increasingly being used parenterally in the treatment of pre-eclampsia. Because of lack of efficacy in a substantial part of our pre-eclamptic patients, we determined the plasma concentrations of ketanserin in 51 pre-eclamptic patients. Population pharmacokinetic parameters were assessed using the iterative two-stage Bayesian population procedure. The influence of individual pharmacokinetic parameters on antihypertensive response, expressed as the attainment of a diastolic blood pressure <or=90 mmHg using ketanserin treatment, was analysed. Almost all plasma concentrations of ketanserin were in or above the therapeutic range. The individual pharmacokinetics of ketanserin in pre-eclamptic patients showed an accurate fit using a three-compartment model. The pharmacokinetic parameters in our pre-eclamptic population were a metabolic clearance (Cl(m)) of 37.9+/-10.86 L/h and volume of distribution (V1) of 0.544+/- 0.188 L/kg, which is comparable with data from healthy volunteers. Despite a considerable inter-individual variation, no correlation was found between differences in pharmacokinetic parameters and antihypertensive response. We conclude that therapeutic plasma levels can be obtained in pre-eclamptic patients with a fixed dosage schedule of ketanserin and differences in antihypertensive responses within a pre-eclamptic population cannot be attributed to pharmacokinetic differences.

• Authors: Lidwien M Hanff, Wil Visser, Erik A P Steegers, Arnold G Vulto
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 19 Issue 5 Pg. 585-90 (Oct 2005) ISSN: 0767-3981 [Print] England
• PMID: 16176338 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Antihypertensive Agents
• Ketanserin

Topics

• Adult
• Antihypertensive Agents (administration & dosage, pharmacokinetics)
• Female
• Humans
• Hypertension (drug therapy, physiopathology)
• Infusions, Intravenous
• Ketanserin (administration & dosage, blood, pharmacokinetics)
• Metabolic Clearance Rate
• Pre-Eclampsia (drug therapy, physiopathology)
• Pregnancy
• Pregnancy Trimester, Third
• Time Factors
• Treatment Outcome